The Water Framework Directive requires the assessment of the ecological status of transitional waters considering the fish component. An original methodology, based on a pressure-impact approach, was established to develop a multimetric fish-based index to characterize the ecological quality of French estuaries. An index of contamination, based on the chemical pollution affecting aquatic systems, was used as a proxy of anthropogenic pressure. The fish metric selection was based on their response to disturbances tested via statistical models (generalized linear models) taking into account sampling strategy and estuarine features. Four metrics, for which discriminating responses to level of pressure were demonstrated, were retained to constitute the estuarine multimetric fish index. This new tool appeared particularly relevant to detect the contamination effects on fish communities in estuaries. It could help managers to take decisions in order to maintain or reach the good status required by the Water Framework Directive for 2015.